Vertebrate gastrulation involves complex coordinated regulated movements of cells and cell layers to establish the axial structures and the general body plan. Adhesion molecules and the components of extracellular matrix participate in this process. However, other components and detailed mechanisms of the control of gastrulation movements remain largely unknown. For instance, perturbation of cell adhesion by interference with function of different cadherins or extracellular matrix proteins (Kim, et al., Development 125, 4681-4691 (1998); Kuhl, et al., Mechanisms of Development 54, 71-82 (1996)) has been shown to lead to certain defects in gastrulation. As such, the elucidation of a protein and its nucleic acid involved in cell adhesion may be useful as diagnostic indicators for certain birth defects.
Adhesion molecules mediate cell to cell and cell to matrix interactions and are essential for numerous physiological and pathological processes. The first step of metastasis is the detachment of the tumor cells from the primary tumor and subsequent access to the circulation such as lymph or blood. Although the exact mechanism is unclear at this time, it has been demonstrated that the loss of certain adhesion molecules, such as certain of the cadherins, is associated with the penetration of tumor cells into other tissues and the increased incidence of metastasis, perhaps by facilitating the detachment of the tumor cells from the primary tumor. Accordingly, the elucidation of a protein and its nucleic acid involved in cell adhesion may be useful as a target for anti-metastatic agents.
The present invention is based upon the discovery of a novel gene family, hereinafter denoted xe2x80x9cthe camello gene familyxe2x80x9d that the inventors believe is involved in embryogenesis and cell adhesion. This discovery may provide useful targets for anti-metastatic agents, as well as diagnostic indicators for birth defects.
Accordingly, the present invention provides a purified and isolated nucleic acid encoding a camello protein. The present invention also provides a vector comprising this nucleic acid and a host cell transformed by this vector. Also provided by the present invention is a nucleic acid probe which hybridizes to nucleic acid encoding camello, a mixture of nucleic acid probes each of which hybridizes to nucleic acid encoding camello and a kit comprising one or more nucleic acid probes which hybridize to nucleic acid encoding camello.
The present invention also provides a method for producing recombinant camello comprising growing a host cell transformed with a vector comprising nucleic acid encoding camello in culture and recovering the recombinant camello from the culture. The present invention further provides a purified camello protein or an analogue thereof, as well as an agent that binds to the camello protein or its analogue, including but not limited to an antibody immunoreactive with camello or an analogue thereof. In addition, the present invention provides a kit comprising an agent that binds to the camello protein.
The present invention also provides a method for screening an agent that binds to the nucleic acid encoding a camello protein comprising contacting the nucleic acid with an agent of interest and assessing the ability of the agent to bind to the nucleic acid. The present invention further provides for a method for screening an agent that inhibits the expression of the nucleic acid encoding a camello protein comprising contacting a cell transformed with a vector comprising the nucleic acid, and assessing the effect of the agent on expression of the nucleic acid. The present invention still further provides a method for screening for an agent that binds to a camello protein or an analogue thereof comprising contacting the protein with an agent of interest and assessing the ability of the agent to bind to the protein.
In addition, the present invention provides a method for determining the aggressiveness of a tumor in a subject comprising detecting abnormal levels of a camello protein in the tumor relative to normal physiological levels of camello in normal tissue. Further, the present invention provides a method for the diagnosis of birth defects comprising detecting abnormal levels of a camello protein in embryological tissue relative to normal physiological levels of camello.
The present invention also provides a recombinant viral vector capable of introducing nucleic acid encoding camello into a target cell such that the target cell expresses camello, the vector comprising (a) nucleic acid of or corresponding to at least a portion of the genome of a virus, the portion being capable of infecting the target cell, and (b) nucleic acid encoding a camello protein operably linked to the viral nucleic acid. Finally, the present invention provides a non-human, transgenic animal model comprising mutated nucleic acid encoding camello incorporated into at least some of the somatic cells of the animal. Additional objects of the present invention will be apparent from the description which follows.